Selenols: a new class of carbonic anhydrase inhibitors

Angeli, Andrea; Tanini, Damiano; Nocentini, Alessio; Capperucci, Antonella; Ferraroni, Marta; Gratteri, Paola; Supuran, Claudiu T.

doi:10.1039/c8cc08562e

Cited by 63 publications

(53 citation statements)

References 35 publications

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“…Commercially available reagents were used as obtained from freshly opened containers without further purification. Aryl selenols 1a-d [32], alkyl selenol 1e [31], and N-thiophthalimides 2 [43][44][45][46][47][48] were prepared according to reported procedures. Spectroscopic data of diselenides 4a-e [26,49] and disulfides 5a-h [30] matched those previously reported in the literature.…”

Section: Methodsmentioning

confidence: 99%

“…However, HMDSS was efficient in the opening of ring strained heterocycles, namely epoxides, episulfides and aziridines, leading to a wide range of β-functionalized selenols, which were stable enough to react with electrophiles under controlled catalytic conditions [31]. Differently substituted stable aryl selenols were also prepared by reduction of the parent diselenides to explore their activity as enzyme inhibitors [32].On the basis of our findings on the behaviour of selenols we report here a new approach for the preparation of selenenylsulfides using N-thiophtalimides as suitable electrophiles.…”

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confidence: 99%

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Towards New Catalytic Antioxidants: A Simple and Mild Synthesis of Selenenylsulfides

Tanini¹,

Bonardi²,

Viglianisi³

et al. 2019

Catalysts

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A new methodology for the synthesis of small molecules containing the S-Se bond is reported. Aryl-and alkyl-selenols react smoothly with N-thiophthalimides to afford the corresponding selenenylsulfides through a clean S N 2 path occurring at the sulfur atom. The reaction proceeds under very mild conditions in DMF in absence of catalysts for most of the substrates. The scope of the reaction was found to be broad, allowing a wide series of selenols and N-thiophtalimides to be efficiently employed in this procedure. Owing to the instability of the S-Se bond, selenenylsulfides exhibited a remarkable tendency to disproportionate to the corresponding symmetric diselenides and disulfides. Preliminary evaluation of the catalytic antioxidant properties of novel selenenylsulfides showed their behaviour as GPx mimics.Catalysts 2019, 9, 333 2 of 11 a second equivalent of GSH, to reform the selenol, together with oxidized glutathione GSSG. The selenenylsulfide, containing the Se-S bridge, represents the key intermediate for the activity of the enzyme [7,[16][17][18][19]. Taking into account the importance of this process, several synthetic approaches to obtain selenated small molecules as enzyme mimics have been developed. However, to the best of our knowledge, a limited number of methods are reported for the preparation of selenenylsulfides. These methods typically exploited the reactivity of diselenides in thiol-diselenide exchange or foresee the reaction of sulfenyl derivatives with thiols [16,17,[20][21][22].It is well established that the Se-S bridge is unstable and undergoes disproportionation reaction to afford diselenides and disulfides. Some examples are reported on selenenylsulfides stabilized by sterically bulky groups or by intramolecular Se . . . Het (N, O) interactions [23].Owing to the interest in these selenium containing compounds, the search for novel procedures to prepare small molecules containing the Se-S unit is of great interest.Our long-dated interest in the chemistry of silyl chalcogenides allowed to disclose novel procedures to access a plethora of sulfur and selenium containing molecules exploiting the nucleophilic behaviour of the chalcogen atom towards various electrophiles [24][25][26][27][28][29]. Recently we reported the reaction of bis(trimethylsilyl)selenide (HMDSS) with N-thiophtalimides as a mild, general metal free procedure for the synthesis of variously substituted disulfides [30].Indeed, despite the interest in the reactivity of selenols as nucleophilic selenium transfer reagents, their use has been critically limited by their instability. However, HMDSS was efficient in the opening of ring strained heterocycles, namely epoxides, episulfides and aziridines, leading to a wide range of β-functionalized selenols, which were stable enough to react with electrophiles under controlled catalytic conditions [31]. Differently substituted stable aryl selenols were also prepared by reduction of the parent diselenides to explore their activity as enzyme inhibitors [32].On the basis of our findings ...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Towards New Catalytic Antioxidants: A Simple and Mild Synthesis of Selenenylsulfides

Tanini¹,

Bonardi²,

Viglianisi³

et al. 2019

Catalysts

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“…Sulfonamides are the main class of zinc-binding CA inhibitors (CAIs), [2,3] but several other classes of inhibitors have also been reported recently, such as the thiols, dithiocarbamates, coumarins, polyamines and selenols among others [30,31]. We have thus included a range of sulfonamides in an initial screening program to find the compounds targeting this new protozoan enzyme.…”

Section: Enzyme K Cat (Smentioning

confidence: 99%

“…We have thus included a range of sulfonamides in an initial screening program to find the compounds targeting this new protozoan enzyme. Sulfonamides, thiols, dithiocarbamates and selenols possess a similar mechanism of action, as they bind to the zinc ion within the active site cavity and substitute the non-protein zinc ligand (the hydroxide ion/water molecule) [2,3,30,31]. Here, we investigated a panel of 24 sulfonamides (compounds 1−24, whose molecular structure is depicted in Figure 1) for their ability to inhibit recombinant SmCA (rSmCA).…”

Section: Enzyme K Cat (Smentioning

confidence: 99%

Sulfonamide Inhibition Studies of an α-Carbonic Anhydrase from Schistosoma mansoni, a Platyhelminth Parasite Responsible for Schistosomiasis

Angeli

Pinteală²,

Maier³

et al. 2020

IJMS

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Schistosomiasis is a debilitating infection provoked by parasitic flatworms called schistosomes. The species Schistosoma mansoni is endemic in Africa, where it causes intestinal schistosomiasis. Recently, an α-carbonic anhydrase (CA, EC 4.2.1.1) was cloned and characterized from this organism and designated as SmCA. The protein is expressed in the tegument (skin) of S. mansoni at the host-parasite interface. Recombinant SmCA possesses high catalytic activity in the CO 2 hydration reaction, similar to that of human CA isoform II with a k cat of 1.2 × 10 6 s −1 and a k cat /K M of 1.3 × 10 8 M −1 ·s −1 . It has been found that schistosomes whose SmCA gene is suppressed using RNA interference are unable to establish a robust infection in mice, suggesting that the chemicals that inhibit SmCA function should have the same debilitating effect on the parasites. In this study, a collection of aromatic/heterocyclic sulfonamides were investigated as possible SmCA inhibitors. Several sulfonamides inhibited SmCA with medium to weak potency (K I values of 737.2 nM−9.25 µM), whereas some heterocyclic compounds inhibited the enzyme with K I values in the range of 124−325 nM. The α-CA from S. mansoni, SmCA, is proposed as a new anti-schistosomiasis drug target.

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“…Selenium, a member of group XVI of the periodic table, is an essential element in the human body with potential antioxidant properties [25]. Selenium-containing compounds and polymers have found applications in many areas, including organic synthesis, biochemistry, semiconductors, and ligand chemistry [26][27][28]. For example, selenium-containing polymers can potentially serve as mild-responsive drug delivery vehicles and artificial enzymes [25].…”

Section: Introductionmentioning

confidence: 99%

A Selenone-Functionalized Polyhedral Oligomeric Silsesquioxane for Selective Detection and Adsorption of Hg2+ ions in Aqueous Solutions

et al. 2019

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Developing novel functional polyhedral oligomeric silsesquioxane (POSS) for various applications is highly desirable. Herein we present the first example of a novel selenone-functionalized POSS (POSS-Se) by treating an imidazolium-containing POSS with selenium powder under mild condition. The structure of POSS-Se was characterized by FT-IR, 1 H NMR, 13 C NMR, 29 Si NMR, and elemental analysis. Acid treatment of POSS-Se results in a hydrophilic red-orange colored solid, which is highly sensitive and selective for the detection of Hg 2+ ions in aqueous solutions by visually observing the color change to pale yellow, and to white. Interestingly, POSS-Se has no activity on this detection. This finding is due to the Se-Se formation by acid-treatment and subsequent coordination-induced cleavage upon the addition of Hg 2+ ions. The detection behavior can be precisely monitored by a "turn-on" fluorescence phenomenon with the limit of detection (LOD) of 8.48 ppb, comparable to or higher than many reported Hg 2+ sensors. Moreover, POSS-Se demonstrates a selective and efficient adsorption of Hg 2+ ions with a maximum capacity of 952 mg g -1 . The value is higher than most reported adsorbents for Hg 2+ ions, typically thiol and/or thioether functional materials, indicating its promise as an efficient adsorbent for the selective removal of Hg 2+ ions from industrial wastewater. This work may open up new horizons for the exploration of selenium-containing functional POSS.

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Selenols: a new class of carbonic anhydrase inhibitors

Abstract: Aryl selenols effectively inhibit carbonic anhydrase.

Cited by 63 publications

References 35 publications

Towards New Catalytic Antioxidants: A Simple and Mild Synthesis of Selenenylsulfides

Towards New Catalytic Antioxidants: A Simple and Mild Synthesis of Selenenylsulfides

Sulfonamide Inhibition Studies of an α-Carbonic Anhydrase from Schistosoma mansoni, a Platyhelminth Parasite Responsible for Schistosomiasis

A Selenone-Functionalized Polyhedral Oligomeric Silsesquioxane for Selective Detection and Adsorption of Hg2+ ions in Aqueous Solutions

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